One (1) of the most difficult problems we face in neuroscience is understanding how neuronal networks process information. Understanding how a network operates depends on knowing what its component cell classes do-that is what their activity patterns are and how they relate to the activity patterns of other cell classes. Here we propose a new method for monitoring activity in neuronal systems. The method combines genetic and optical imaging techniques. Genetics allows specific cell classes to be targeted, and optical imaging allows the activity of the cells in each class to be monitored with high spatial and temporal resolution. The method is built around a marker protein, and the specific aims are as follows: Aims 1 and 2 focus on building compounds that react with the protein to produce activity-indicators, and Aim 3 focuses on testing the performance of the indicators (measuring their selectivity, dynamic range and kinetics). This tool has broad applications, both basic and applied, from monitoring cell-to-cell communication in the developing and mature nervous system to monitoring the actions (effectiveness and selectivity) of neuroactive drugs. [unreadable] [unreadable]